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CardioSource WorldNews | Athletes with Bradycardia
How slow is too slow?
In athletes, a normal electrocardiogram (ECG) is the anomaly. In Italy, where there is a nationwide screening program for conditions causing sudden cardiac death, the proportion of individuals 14 to 35 years of age with a completely normal ECG was 42.5% in nonathletes but only 2.6% in athletes (p < 0.001).1 The paper, published in JACC, demonstrated that trained athletes show ECG changes such as sinus bradycardia, first-degree atrioventricular block, and early repolarization, all of which can result from physiological adaptation of the cardiac autonomic nervous system to athletic conditioning (e.g., increased vagal tone and/or withdrawal of sympathetic activity).
The ECGs of trained athletes often exhibit pure voltage criteria (i.e. based only on QRS amplitude measurements) for left ventricular hypertrophy (LVH) that reflect physiological LV remodeling with increased LV wall thickness and chamber size.
Resting sinus bradycardia, as defined by a heart rate < 60 bpm, is the most common ECG pattern in athletes, occurring in 57.6% of 4,081 athletes versus 26.1% of the 7,764 nonathletes in the aforementioned Italian study by Hariharan Raju, MBBS, St. George’s University of London, UK, and colleagues. Prevalence varied depending on the type of sport and the level of training/competition. Sports that require high endurance, such as cycling, cross-country skiing, and rowing/canoeing are each significantly associated with a higher rate and greater extent of physiological ECG changes compared with participation in sports that require more strength and speed and relatively less endurance.
In highly trained athletes, Pelliccia and others have noted that marked bradycardia < 30 bpm and asymptomatic sinus pauses > 2 seconds are not uncommon during 24-h ECG, particularly during sleep.2
When the Abnormal is Normal
When Dr. Raju and his associates reported their large analysis in JACC in 2014, they demonstrated that one in five young people (athletes or nonathletes) have group 2 ECG patterns, meaning ECG patterns suggestive of cardiomyopathy or some sort of structural cardiac abnormality.1 The low incidence of sudden cardiac death in young people suggests that, in most instances, such patterns are non-specific. That is important to know given that the European guidelines recommend transthoracic echocardiography in individuals with group 2 ECG patterns.
According to Dr. Raju, their findings have significant implications on the feasibility and cost effectiveness of nationwide screening programs for CVD in young nonathletes and athletes alike, on the basis of current guidelines.
As one practitioner put it recently, when looking at a young athlete’s ECG “You’ve got minnows that are actually sharks and sharks that are actually minnows.” Sanjay Sharma, MD, a professor of inherited cardiac disease and sports cardiology at St. George’s University of London, UK, feels that doctor’s pain. “An athlete’s ECG is divided into two main categories: one that reflects increased vagal tone and the other that reflects increased chamber enlargement. And we know that about 80% of athletes would have an ECG that falls into one or both of those categories.”
These changes include sinus bradycardia, sinus arrhythmia, first degree AV block, and criteria for left ventricular hypertrophy, the early repolarization pattern and incomplete right bundle branch block. Dr. Sharma added, “These are normal changes. However, many athletes express very profound repolarization changes that may overlap with disease processes. The current criteria for ECG interpretation are relatively conservative and many many athletes end up having false positive tests. That is the Achilles heel of the ECG.”
What advice do the current guidelines offer? As Pelliccia and others noted in their recommendations for interpreting a 12-lead ECG in the athlete,2 only profound sinus bradycardia and/or marked sinus arrhythmia (heart rate < 30 bpm and/or pauses ≥ 3 seconds during wake hours) need to be distinguished from sinus node disease. Sino-atrial node dysfunction can be reasonably excluded by demonstrating that: 1) symptoms such as dizziness or syncope are absent; 2) sinus bradycardia is easily overcome with exercise, suggesting that high vagal tone causes slowing of the sinoatrial node; and 3) bradycardia reverses with training reduction or discontinuation. (Note: it’s not just exercise: heart rate also normalizes during sympathetic maneuvers or with drugs, with preservation of maximal heart rate.)
The ESC pacing guidelines also address this issue,3 noting “it is crucial” to distinguish between physiological bradycardia, due to autonomic conditions or training effects, and inappropriate bradycardia that requires permanent cardiac pacing. For example, sinus bradycardia, even when it is 40 to 50 bpm while at rest or as slow as 30 bpm while sleeping, is accepted as a physiological finding that does not require cardiac pacing in trained athletes.
In brief, according to Dr. Raju, if the patient is not symptomatic, there is no such thing as “too slow.” Having said that, he reminds clinicians to not forget the differential, considering there are other potential reasons for bradycardia such as Lyme disease, an inherited disease, or a structural heart disease.
- Chandra N, Bastiaenen R, Papadakis M, et al. J Am Coll Cardiol. 2014;63:2028-34.
- Corrado D, Pelliccia A, Heidbuchel H, et al. Eur Heart J. 2010;31:243-59.
- Brignole M, Auricchio A, Baron-Esquivias G, et al. Eur Heart J. 2013;34:2281-329.
Risk Prediction After Age 75
There are nearly 20 million Americans who are 75 years of age or older (based on the 13.7 million people who are 75 to 84 years old and the 6.0 million in the U.S. who are 85 or older).1 By age 75, most people are at significant risk for atherosclerotic cardiovascular disease (ASCVD), but competing risk for mortality from non-CVD causes is high. For appropriate risk estimation of elderly patients, it’s important to consider competing risks for non-CVD mortality.
Donald M. Lloyd-Jones, MD, FACC, is the director of Northwestern University Clinical and Translational Sciences Institute in Chicago and co-chair of the ACC/AHA guideline on assessing cardiovascular risk.2 He acknowledges that, as we get older, some risk factors lose steam as predictors, especially cholesterol. He notes that people susceptible to atherosclerosis have high cholesterol levels by the time they are in their mid-70s or older. Prevalence of atherosclerosis is very high, so focus should be on target organ damage and triggering of events, in the context of life expectancy and patient goals.
Recalculating How Risk Gets Calculated
Without calculating a risk score, Dr. Lloyd-Jones says the average 75-year-old has a 10-year ASCVD risk of at least 30%. How does he figure that? Easy, life expectancy at age 75 is a little more than a decade for men (10.7 years to be precise) and slightly longer for women (12.6 years). There is no math necessary to know the epidemiology: CHD and stroke together account for 30% of deaths at this age and that’s just the fatal events.
As noted above, competing risks must be taken into account for proper risk estimation. Dr. Lloyd-Jones and colleagues published on this concept of assessing patients within a competing risks framework.3 They put it this way: “Competing risk models estimate which specific events are more likely to occur first for various populations; this ability to understand risks for multiple different outcomes at a given point in time may be clinically useful, because it affords patients and clinicians a more accurate sense of real-life risks for first events.”
As for risk factors that are losing steam at this point in life, Dr. Lloyd-Jones looks at it this way: “By older age, you have been marinating your arteries in plenty of apolipoprotein B-containing particles, regardless of your LDL-cholesterol level.” With older age, he said, there is no “normal” LDL level; hence, you see an MI in a person with “normal” cholesterol.
Given the high prevalence of ASCVD, Dr. Lloyd-Jones said we no longer care so much about risk factors in patients after age 75. It is more about disease burden, he said, and triggering events. Granted, he said, triggering is tough to predict. At this age, one issue is “instantaneous risk.” For example, will it snow tomorrow and your patient have to shovel? Will there be something else to make their blood pressure spike?
In the near future, he said, he can envision a risk score that is competing-risk-adjusted, age-specific, and inclusive of appropriate risk factors and biomarkers of target organ damage or disease burden. In any event, he predicts that patient-clinician discussion will still be crucial.
Finally, a new paper leaves us with reason for optimism. As this issue of CSWN was going to press, a paper was published identifying a group of “adapter” older adults who were more vigorous than expected, based on their disease burden.4 Compared to a reference group of “expected agers,” these adapters did significantly better in terms of years of able life and years of self-reported healthy life. They also lived longer than expected based on their disease burden.
This four-city U.S. study suggests that we need to learn a lot more about these “adapters,” who could have unique characteristics or perhaps some undefined coping mechanism. Studying these individuals further might reveal how these older adults manage to “compress morbidity and live longer.”
- [No authors listed] National Center for Health Statistics. Health, United States, 2015: With Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD. 2016.
- Goff DC, Jr., Lloyd-Jones DM, Bennett G, et al. J Am Coll Cardiol. 2014;63:2935-59.
- Feinstein M, Ning H, Kang J, et al. Circulation. 2012;126:50-9.
- Sanders JL, Arnold AM, Hirsch CH, et al. J Am Geriatr Soc. 2016;64:1242-9.
- Why Exercise Works in Heart Failure with Preserved Ejection Fraction
When you see the phrase “heart failure with preserved ejection fraction” (and its awkward abbreviation HFpEF), you can be forgiven if your eyes want to dart ahead to the next page to check the next topic. It’s as much an understatement to say that HFpEF is frustrating to manage as it is to say that the Grand Canyon is quite the crevice.
Sheldon E. Litwin, MD, FACC, understands this, acknowledging that HFpEF is difficult to understand, difficult to diagnose, and—it would seem—impossible to treat. Dr. Litwin is a professor of cardiology at the Medical University of South Carolina, Ralph Johnson VA Medical Center, in Charleston, SC. He points to “all” kinds of problems:
- “All” large HFpEF trials have had problems enrolling patients.
- “All” trials have had fewer endpoints than expected.
- “All” trials have failed to show efficacy for the primary endpoint.
Why, he asks? Wrong patients? Wrong disease? Wrong diagnosis? Wrong drugs? Yes, and it might be wrong if you jump ahead to the next article because Dr. Litwin has some important insights.
Don’t Blame the Heart
The heart may not even be the primary problem in HFpEF. Dr. Litwin points out that brain natriuretic peptide is < 100 pg/ml (considered the cut-off for increased risk of cardiac events) in one-third of HFpEF patients. Obesity is often an issue, as is obstructive sleep apnea, chronic kidney disease, anemia, and—in a word—muscle.
Think about how we increase oxygen utilization during exercise. Increased heart rate (100% to 300%), of course, and the loss of this mechanism is the main reason for decreased athletic performance with age. Add in the fact that beta-blockers limit heart rate reserve and oxygen becomes a challenge inhibiting life in general and exercise in particular. Likewise, aging causes a crippling of one of the key means for boosting oxygen utilization during exercise.
Exercise does increase stroke volume (by about 30%), making it one way for the body to increase oxygen utilization, along with increasing peripheral oxygen extraction (150% to 300%).
If you compare elite athletes versus age-matched nonathletes, there is no difference in peak heart rate, but there is mildly higher stroke volume in the athletes and—importantly—higher and more efficient muscle oxygen utilization compared to the nonathletes.
This may help explain the results of a meta-analysis of randomized clinical trials (RCT) evaluating exercise training in patients with HFpEF.1 Compared to controls, exercise training was associated with clinically significant improvements in cardiorespiratory fitness and QOL without significant changes in LV systolic or diastolic function. In another recent study, investigators reported, contrary to their hypothesis, that 1 year of endurance training failed to show any favorable effects on cardiovascular stiffness or function in HFpEF.2 (It should be noted that this was the first study with invasive pressure measurements in seven patients and 13 controls.)
Dr. Litwin also mentioned that if you look across the available literature, training in patients with HFpEF leads to minimal or no change in peak heart rate and no change in peak blood pressure compared to controls. Arterial stiffness is increased in HFpEF, but there have been mixed findings on vasodilator reserve in HFpEF: there is some evidence that exercise training in HFrEF (HF with reduced ejection fraction) does improve arterial function. Also, exercise does not seem to impact brachial flow mediated dilatation (endothelial function) or carotid distensibility.
While improved diastolic function or diastolic filling was presumed to be one reason why exercise might work in HFpEF, that did not seem to be the case. So, what else might apply? The list of potential factors includes improved chronotropic responsiveness, improved endothelial function (reduced afterload), reduced inflammation, metabolic adaptations (such as more efficient energy production), and skeletal muscle adaptations.
Let’s look at the problem from a different perspective: what are the mechanisms of exercise intolerance in HFpEF? Investigators performed upright cardiopulmonary exercise testing with hemodynamic monitoring in patients with HFpEF, elevated pulmonary capillary wedge pressure, and exercise intolerance. Dhakal et al.3 found that a peripheral limitation was the most important cause of reduced aerobic capacity, whereas impaired cardiac output had less impact. This finding is consistent with other studies that indirectly estimated oxygen extraction.
In an accompanying editorial comment, William C. Little, MD, and Barry A. Borlaug, MD, FACC, noted that the delivery of oxygen to contracting muscles is essential to perform aerobic exercise.4 Optimum oxygen delivery requires oxygenation of the blood in the lungs, normal oxygen carrying capacity of the blood, adequate cardiac output that is appropriately distributed to match regional demands, and adequate tissue extraction of oxygen from the blood. Normal adults can increase oxygen consumption (Vo2) more than six-fold during exercise by increasing cardiac output (because of a faster heart rate and enhanced stroke volume) and by augmenting oxygen extraction producing a fall in mixed venous oxygen content, thereby increasing the difference between arterial and venous oxygen content. Measuring Vo2 during exercise provides a powerful method to objectively assess the degree of functional limitation and prognosis in patients with HFrEF. The study by Dhakal et al. confirms that the cause of the reduction in peak Vo2 in patients with HFpEF is predominantly (but not exclusively) because of an inadequate increase in cardiac output during exercise.
Thus, the evidence suggests that improving abnormal O2 extraction—for example, through exercise—might be an important therapeutic target in the notoriously difficult-to-treat patients with HFpEF. And it seems exercise is the key; while most studies have looked at aerobic exercise, resistance training as been evaluated, too, although there is really not enough evidence available at the present time to say one is superior to the other.
Little and Borlaug added, the data also suggest other approaches to therapy: For example, “inorganic nitrates can improve vascular conductance and oxygen delivery to skeletal muscle during exercise. An alternative approach might be to modify the allosteric regulation of hemoglobin to allow for greater oxygen dissociation in the muscle. In addition, training may enhance exercise tolerance in HFpEF without producing an improvement in systolic or diastolic function. It may be that exercise testing can be used to identify the primary mechanisms of exercise intolerance in the individual patient, potentially allowing for more tailored therapies in HFpEF.”
Here is how Dr. Litwin interprets the data: there are intrinsic abnormalities of skeletal muscle structure, biochemistry and metabolism in HFpEF. Exercise increases muscle oxygen uptake, perhaps via mitochondrial biogenesis, muscle fiber type, increased oxidative enzymes, and increased capillary density.
Put another way, a heart-centric view has not been helpful in the treatment of HFpEF, with failure to benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists, beta-blockers, digoxin, phosphodiesterase type 5 inhibitors, and nitrates. Therefore, when considering HFpEF, think outside the heart.
- Pandey A, Parashar A, Kumbhani DJ, et al. Circ Heart Fail. 2015;8:33-40.
- Fujimoto N, Prasad A, Hastings JL, et al. Am Heart J. 2012;164:869-77.
- Dhakal BP, Malhotra R, Murphy RM, et al. Circ Heart Fail. 2015;8:286-94.
- Little WC, Borlaug BA. Circ Heart Fail. 2015;8:233-5.
|Read the full August issue of CardioSource WorldNews at ACC.org/CSWN|
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